Nanoparticle (“NP”) applications in medical diagnostics and other investigative and therapeutic technologies represent novel and improved modes of in-situ, internal, cell and tissue diagnostics and targeted drug delivery. Nanoparticles can be administered systemically to a subject, such as a human body. The small nanometer size of nanoparticles allows nanoparticle entry into internal subsurface regions and functional areas that cannot be achieved and observed by conventional means.
Magnetic nanoparticles (“MNPs”) can be directed to a particular target in a subject through the use of an external magnetic field and/or via the target's systemic system. Accordingly, magnetic nanoparticles have been used in non-invasive, in situ diagnostics, such as, for a non-limiting example, magnetic resonance imaging (“MRI”). In addition, magnetic nanoparticles have been used in targeted drug delivery applications. For example, a therapeutic agent can be attached to a surface of a targeted nanoparticle. Alternatively, a therapeutic agent can be contained within a polymer coating encapsulating an intrinsic core of the targeted nanoparticle. Ultimately, the magnetic nanoparticles can be localized in the systemic system through the application of the magnetic field and/or ultrasound and/or the natural systemic flow within the system.
The enhanced permeability and retention (“EPR”) effect, where molecules of certain sizes tend to accumulate notably more in tumor tissues than in normal tissues, can be related to nanoparticle applications. Only molecules and accordingly, nanoparticles, of certain sizes can enter or permeate or be retained by cancerous cells and tissue. The EPR effect is one of the most exploitable known dynamics in the delivery of systemically administered drugs to cancerous tissues, because the dynamic relates to the anatomical and pathophysiological features of tumor blood vessels. Macromolecular cancer drug developers identify the EPR effect as the predominant mechanism for targeting drugs to solid tumors. Personalized medicine approaches can extend to noninvasive methods for predicting and measuring therapeutic responses based on the exploitability of the EPR effect.
To date, the EPR effect has not been sufficiently exploited in nanoparticle medical applications because typically the applications employ randomly sized distributions of nanoparticles and fail to correlate nanoparticle size to EPR effect for maximum entry and retention of nanoparticles by cancerous cells and tissue. In addition, typical nanoparticle medical applications fail to consider that the EPR effect is not homogeneous and can vary from patient to patient, tumor to tumor, and even within a single tumor.
Thus, there is a need to develop systems and methods for using predetermined, closely sized and/or non-randomly sized distributions of nanoparticles to provide greater insight into cell and tissue functioning, to improve the efficiency and efficacy of EPR related diagnostics and therapies, and to reduce side effects compared to conventional treatments.